Brachytherapy is a general term covering medical treatment which involves the placement of a radioactive source near a diseased tissue and may involve the temporary or permanent implantation or insertion of a radioactive source into the body of a patient. The radioactive source is thereby located in proximity to the area of the body which is being treated. This has the advantage that a high dose of radiation may be delivered to the treatment site with relatively low dosages of radiation to surrounding or intervening healthy tissue.
Brachytherapy has been proposed for use in the treatment of a variety of conditions, including arthritis and cancer, for example breast, brain, liver and ovarian cancer and especially prostate cancer in men (see for example J. C. Blasko et al., The Urological Clinics of North America, 23, 633-650 (1996), and H. Ragde et al., Cancer, 80, 442-453 (1997)). Prostate cancer is one of the most common forms of malignancy in men in the USA, with more than 44,000 deaths in 1995 alone. Treatment may involve the temporary implantation of a radioactive source for a calculated period, followed by its removal. Alternatively, the radioactive source may be permanently implanted in the patient and left to decay to an inert state over a predictable time. The use of temporary or permanent implantation depends on the isotope selected and the duration and intensity of treatment required.
Permanent implants for prostate treatment comprise radioisotopes with relatively short half lives and lower energies relative to temporary sources. Examples of permanently implantable sources include iodine-125 or palladium-103 as the radioisotope. The radioisotope is generally encapsulated in a casing such as titanium to form a “seed” which is then implanted. Temporary implants for the treatment of prostate cancer may involve iridium-192 as the radioisotope.
Conventional radioactive sources for use in brachytherapy include so-called seeds, which are sealed containers, for example of titanium, containing the radioisotope within a sealed chamber but permitting radiation to exit through the container/chamber walls (U.S. Pat. Nos. 4,323,055 and 3,351,049). Such seeds are only suitable for use with radioisotopes which emit radiation which can penetrate the chamber/container walls. Therefore, such seeds are generally used with radioisotopes which emit γ-radiation or low-energy X-rays, rather than with β-emitting radioisotopes.
For ease of administration of such sources, a number of systems have been proposed. U.S. Pat. No. 4,815,449 discloses a substantially non-deflecting, linear, elongated member for insertion in tumours and made of a bioabsorbable material in the form of a needle or thin pointed cylinder with a plurality of radioactive seeds disposed therein in a predetermined array.
U.S. Pat. No. 5,460,592 discloses a method and apparatus for transporting a radioactive device. The device comprises a flexible, elongated woven or braided bio-absorbable carrier material having spaced radioactive seeds disposed therein. On heating, the carrier material holding the seeds becomes semi-rigid. A length of the semi-rigid carrier material with radioactive seeds disposed therein may then be loaded into a conventional, hollow metal dispensing needle or applicator cartridge which is used to implant the radioactive seeds into or contiguous to the treatment site, for example a tumour.
A commercial product consisting of iodine-125 seeds regularly spaced at between 0.6 and 1.2 cm centre to centre inside a braided, semi-rigid bioabsorbable suture material is available from Medi-Physics Inc. under the trade name I-125 RAPID Strand™. This product may be used to treat conditions such as head and neck cancers, including those of the mouth, lips and tongue, brain tumours, lung tumours, cervical tumours, vaginal tumours and prostate cancer.
One advantage of this type of semi-rigid carrier is that the radioactive seeds are implanted or inserted into a patient with a pre-determined known spacing, depending on their separation in the carrier material. The bioabsorbable material is then slowly absorbed into the patient's body to leave the spaced seeds in position. This predetermined spacing and the semi-rigid nature of the carrier aids a physician in calculating both the total radiation dose and the dose profile which will be delivered by the seeds inside a patient's body, and also aids in accurate placement of the seeds. In addition, more than one seed is implanted at once, so lessening the time taken for implantation over that required for the placement of individual loose seeds. The risk of seed migration away from the site of implantation is also reduced (Tapen et al., Int. J. Radiation Oncology Biol. Phys., vol. 42(5), pages 1063-1067, 1998).
Radioactive sources according to U.S. Pat. Nos. 4,815,449 and 5,460,592 use as little bioabsorbable material as possible to ease absorption but the use of such thin or flexible material has a number of disadvantages. For example, to ensure that the carrier is rigid enough to withstand insertion into the patient's tissues, the carrier material holding the radioactive seeds is stiffened by a heating step during the manufacturing process. However, excessive heat may damage the carrier material, and strict control of the heating and cooling process is critical so as to change the crystalline structure of the carrier material sufficiently to cause stiffening but without causing burning. Even when stiffness is maximised within the possibilities existing within U.S. Pat. No. 5,460,592, the carrier material is not sufficiently rigid to fully guard against jamming of the carrier within the dispensing needle or applicator when in clinical use. Jamming of the carrier within a needle is generally irreversible, so that the needle then has to be disposed of, taking into account the fact that it is now “hot” due to the presence of radioactive seeds. Any adventitious entry of blood and other body fluids into the needle can cause the bioabsorbable material to swell, and strands of the material to fray which also causes jamming of the dispensing needle (Butler et al., Radiation Oncology Investigations 4:48-49, 1996). It has, therefore, become common practice for physicians to “plug” the needle in order to prevent the entry of body fluids into the needle during administration. However, if the needles are not well plugged, jamming may still occur. Conversely, jamming can be caused by use of too much plug material or a plug of a very stiff nature which is not easily displaced from the tip of the needle.
The manufacturing process disclosed in U.S. Pat. No. 5,460,592 is also very labour intensive and does not lend itself easily to automation. In addition, each carrier must be visually examined after the stiffening step to ensure that the seeds are securely retained in the braided bioabsorbable material.
Other radioactive members comprise a hollow tube of carrier material (see, for example, U.S. Pat. No. 4,815,449 and EP 0,466,681). In such radioactive members, the position of the radioactive sources within the carrier material may be maintained by the contact and/or elasticity of the carrier material or by introducing non-radioactive fillers or “spacers” into the regions between the radioactive sources. However, the manufacture of such radioactive members is non-trivial, requiring three separate materials (carrier material, radioactive sources and non-radioactive spacers) and the careful assembly of the three in the correct sequence.
There is, therefore, a need for an improved radioactive member which has one or more of the following advantages: provides a more rigid framework, is more resilient to consumer handling, is easier to use and which does not suffer from all the disadvantages of the known sources. Preferably, such an improved radioactive member can be produced using an automated manufacturing process.